Incidental Mutation 'R1800:Map4k4'
ID 202998
Institutional Source Beutler Lab
Gene Symbol Map4k4
Ensembl Gene ENSMUSG00000026074
Gene Name mitogen-activated protein kinase kinase kinase kinase 4
Synonyms 9430080K19Rik, Nik
MMRRC Submission 039830-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1800 (G1)
Quality Score 225
Status Not validated
Chromosome 1
Chromosomal Location 39940073-40065470 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 40062620 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Lysine at position 1195 (T1195K)
Ref Sequence ENSEMBL: ENSMUSP00000141400 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000163854] [ENSMUST00000168431] [ENSMUST00000192509] [ENSMUST00000193682] [ENSMUST00000195259] [ENSMUST00000195636] [ENSMUST00000195860]
AlphaFold no structure available at present
Predicted Effect probably damaging
Transcript: ENSMUST00000163854
AA Change: T1195K

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000126961
Gene: ENSMUSG00000026074
AA Change: T1195K

DomainStartEndE-ValueType
S_TKc 25 289 6.87e-95 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 687 698 N/A INTRINSIC
low complexity region 721 747 N/A INTRINSIC
low complexity region 754 763 N/A INTRINSIC
low complexity region 811 837 N/A INTRINSIC
low complexity region 891 904 N/A INTRINSIC
low complexity region 919 929 N/A INTRINSIC
CNH 970 1268 2.76e-127 SMART
Predicted Effect unknown
Transcript: ENSMUST00000168431
AA Change: T1145K
SMART Domains Protein: ENSMUSP00000129796
Gene: ENSMUSG00000026074
AA Change: T1145K

DomainStartEndE-ValueType
S_TKc 25 289 6.87e-95 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 633 644 N/A INTRINSIC
low complexity region 667 693 N/A INTRINSIC
low complexity region 700 709 N/A INTRINSIC
low complexity region 757 783 N/A INTRINSIC
low complexity region 837 850 N/A INTRINSIC
low complexity region 865 875 N/A INTRINSIC
CNH 916 1214 2.76e-127 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000191657
Predicted Effect unknown
Transcript: ENSMUST00000192509
AA Change: T1141K
SMART Domains Protein: ENSMUSP00000141665
Gene: ENSMUSG00000026074
AA Change: T1141K

DomainStartEndE-ValueType
S_TKc 25 289 6.87e-95 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 633 644 N/A INTRINSIC
low complexity region 667 693 N/A INTRINSIC
low complexity region 700 709 N/A INTRINSIC
low complexity region 757 783 N/A INTRINSIC
low complexity region 837 850 N/A INTRINSIC
low complexity region 865 875 N/A INTRINSIC
CNH 916 1214 2.76e-127 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000193682
AA Change: T1128K

PolyPhen 2 Score 0.931 (Sensitivity: 0.81; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000141862
Gene: ENSMUSG00000026074
AA Change: T1128K

DomainStartEndE-ValueType
S_TKc 25 289 6.87e-95 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 556 567 N/A INTRINSIC
low complexity region 590 616 N/A INTRINSIC
low complexity region 623 632 N/A INTRINSIC
low complexity region 680 706 N/A INTRINSIC
low complexity region 785 814 N/A INTRINSIC
low complexity region 824 837 N/A INTRINSIC
low complexity region 852 862 N/A INTRINSIC
CNH 903 1201 2.76e-127 SMART
Predicted Effect unknown
Transcript: ENSMUST00000195259
AA Change: T1115K
SMART Domains Protein: ENSMUSP00000142056
Gene: ENSMUSG00000026074
AA Change: T1115K

DomainStartEndE-ValueType
S_TKc 25 289 6.87e-95 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 610 621 N/A INTRINSIC
low complexity region 644 670 N/A INTRINSIC
low complexity region 677 686 N/A INTRINSIC
low complexity region 731 757 N/A INTRINSIC
low complexity region 811 824 N/A INTRINSIC
low complexity region 839 849 N/A INTRINSIC
CNH 890 1188 2.76e-127 SMART
Predicted Effect unknown
Transcript: ENSMUST00000195636
AA Change: T1179K
SMART Domains Protein: ENSMUSP00000141613
Gene: ENSMUSG00000026074
AA Change: T1179K

DomainStartEndE-ValueType
S_TKc 25 289 3.4e-97 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 610 621 N/A INTRINSIC
low complexity region 644 670 N/A INTRINSIC
low complexity region 677 686 N/A INTRINSIC
low complexity region 731 757 N/A INTRINSIC
low complexity region 836 865 N/A INTRINSIC
low complexity region 875 888 N/A INTRINSIC
low complexity region 903 913 N/A INTRINSIC
CNH 954 1252 1.4e-129 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000195860
AA Change: T1195K

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000141400
Gene: ENSMUSG00000026074
AA Change: T1195K

DomainStartEndE-ValueType
S_TKc 25 289 6.87e-95 SMART
low complexity region 318 342 N/A INTRINSIC
coiled coil region 357 494 N/A INTRINSIC
low complexity region 503 512 N/A INTRINSIC
low complexity region 687 698 N/A INTRINSIC
low complexity region 721 747 N/A INTRINSIC
low complexity region 754 763 N/A INTRINSIC
low complexity region 811 837 N/A INTRINSIC
low complexity region 891 904 N/A INTRINSIC
low complexity region 919 929 N/A INTRINSIC
CNH 970 1268 2.76e-127 SMART
Coding Region Coverage
  • 1x: 97.4%
  • 3x: 96.8%
  • 10x: 95.0%
  • 20x: 91.2%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for disruptions in this gene die as embryos around day E9.5-10.5. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 92 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1110002E22Rik A G 3: 137,772,479 (GRCm39) K556R probably damaging Het
4933406P04Rik A T 10: 20,186,893 (GRCm39) probably benign Het
Acmsd C A 1: 127,687,493 (GRCm39) Y258* probably null Het
Adgrf5 A T 17: 43,761,973 (GRCm39) I1223F probably damaging Het
Afp C T 5: 90,638,655 (GRCm39) P6S probably benign Het
Agap2 C A 10: 126,927,540 (GRCm39) H1120Q probably damaging Het
Angpt1 A G 15: 42,375,800 (GRCm39) V152A probably damaging Het
Ankrd1 A T 19: 36,096,759 (GRCm39) F23I probably damaging Het
Armc12 T C 17: 28,757,869 (GRCm39) S334P possibly damaging Het
Arnt2 C A 7: 83,924,583 (GRCm39) D415Y probably damaging Het
Cacna1s G T 1: 136,004,592 (GRCm39) V131L probably benign Het
Cacna2d2 T C 9: 107,404,632 (GRCm39) V1141A possibly damaging Het
Cfap61 T C 2: 145,884,542 (GRCm39) L580P probably damaging Het
Chga A T 12: 102,522,164 (GRCm39) S23C probably damaging Het
Chrna5 A G 9: 54,912,159 (GRCm39) T320A probably damaging Het
Col17a1 G T 19: 47,639,301 (GRCm39) N1081K possibly damaging Het
Cox7b2 A T 5: 71,600,406 (GRCm39) C51S possibly damaging Het
Cstdc3 T A 16: 36,132,895 (GRCm39) D57E probably damaging Het
Cwc22 A T 2: 77,759,797 (GRCm39) D83E possibly damaging Het
D130043K22Rik A C 13: 25,067,877 (GRCm39) D871A probably damaging Het
Dab2 A T 15: 6,464,948 (GRCm39) M361L probably benign Het
Dnah11 A C 12: 117,880,523 (GRCm39) Y3866D probably damaging Het
Dnmbp A G 19: 43,890,159 (GRCm39) I536T probably benign Het
Ehmt1 A T 2: 24,774,302 (GRCm39) S43R probably damaging Het
Ercc5 T C 1: 44,212,540 (GRCm39) L666P probably benign Het
F5 A G 1: 164,010,403 (GRCm39) H378R probably damaging Het
Fat2 A T 11: 55,174,718 (GRCm39) N1998K probably damaging Het
Fbxo28 T C 1: 182,169,099 (GRCm39) D13G unknown Het
Fras1 T C 5: 96,857,741 (GRCm39) S2012P probably benign Het
Gm5624 T A 14: 44,799,302 (GRCm39) N41I probably damaging Het
Gm8104 A G 14: 42,959,028 (GRCm39) I73V possibly damaging Het
Gpr141b T C 13: 19,913,849 (GRCm39) noncoding transcript Het
Gpr68 G A 12: 100,845,167 (GRCm39) P126S probably damaging Het
Gucy1a2 A T 9: 3,582,685 (GRCm39) T156S possibly damaging Het
Hacl1 T A 14: 31,336,221 (GRCm39) Y429F probably damaging Het
Haus3 A C 5: 34,320,916 (GRCm39) L510R probably damaging Het
Helq C T 5: 100,921,990 (GRCm39) G738D probably benign Het
Hsd3b2 G C 3: 98,619,553 (GRCm39) P131A probably damaging Het
Il22ra1 G T 4: 135,475,471 (GRCm39) C247F probably benign Het
Ivl T C 3: 92,479,891 (GRCm39) E58G unknown Het
Kcnk9 G T 15: 72,417,948 (GRCm39) Q61K probably benign Het
Kremen1 CGGG CGGGGGG 11: 5,151,791 (GRCm39) probably benign Het
Loxhd1 G T 18: 77,490,198 (GRCm39) A1314S probably damaging Het
Lratd1 T C 12: 14,200,226 (GRCm39) Y167C probably damaging Het
Lrba A G 3: 86,259,175 (GRCm39) I1397V probably benign Het
Lrig3 T A 10: 125,832,920 (GRCm39) probably null Het
Lrrc36 A G 8: 106,176,397 (GRCm39) D378G probably damaging Het
Lrrc49 G A 9: 60,505,474 (GRCm39) T527I probably damaging Het
Mrps33 G A 6: 39,779,429 (GRCm39) R89C probably damaging Het
Mtor T C 4: 148,547,349 (GRCm39) V444A probably benign Het
Myh2 A G 11: 67,079,764 (GRCm39) E1046G probably damaging Het
Myo15b G T 11: 115,771,335 (GRCm39) probably null Het
Myo5c T C 9: 75,153,446 (GRCm39) Y111H probably damaging Het
Ncoa4-ps A T 12: 119,225,506 (GRCm39) noncoding transcript Het
Ndufv2 G C 17: 66,390,481 (GRCm39) T163R probably damaging Het
Nf1 A G 11: 79,444,794 (GRCm39) N373S possibly damaging Het
Nwd2 A G 5: 63,962,917 (GRCm39) M834V probably benign Het
Ogfod2 T C 5: 124,253,019 (GRCm39) V343A probably damaging Het
Or11g2 C T 14: 50,856,143 (GRCm39) L155F probably benign Het
Or11j4 C A 14: 50,630,786 (GRCm39) S191* probably null Het
Or3a1b A T 11: 74,012,234 (GRCm39) T40S probably benign Het
Or4c115 T A 2: 88,928,050 (GRCm39) T74S probably benign Het
Or51ag1 T C 7: 103,155,248 (GRCm39) I302V possibly damaging Het
Or52ab2 T A 7: 102,969,621 (GRCm39) M1K probably null Het
Or8g34 A T 9: 39,373,410 (GRCm39) I228F probably damaging Het
Parp1 T A 1: 180,428,091 (GRCm39) probably null Het
Ppp3ca A T 3: 136,640,792 (GRCm39) I448F probably damaging Het
Prss44 T C 9: 110,646,272 (GRCm39) V333A probably damaging Het
Pxk C T 14: 8,151,507 (GRCm38) R441* probably null Het
Rars1 A C 11: 35,716,822 (GRCm39) D231E probably benign Het
Rfc1 T C 5: 65,421,722 (GRCm39) Y1059C probably damaging Het
Rilpl1 T A 5: 124,652,719 (GRCm39) I2F probably damaging Het
Sarm1 G T 11: 78,381,820 (GRCm39) A221E possibly damaging Het
Serpina3f A G 12: 104,183,665 (GRCm39) T176A probably damaging Het
Slc22a20 T C 19: 6,035,695 (GRCm39) E131G probably benign Het
Slc26a11 T C 11: 119,263,979 (GRCm39) V343A probably damaging Het
Slc2a4 A G 11: 69,837,133 (GRCm39) I9T probably benign Het
Slc39a6 G T 18: 24,718,259 (GRCm39) D599E probably damaging Het
Slc5a6 G T 5: 31,198,020 (GRCm39) S285* probably null Het
Spata9 A G 13: 76,125,760 (GRCm39) H81R probably benign Het
St7l A G 3: 104,826,812 (GRCm39) E436G probably damaging Het
Tecrl A G 5: 83,427,077 (GRCm39) I357T probably damaging Het
Thop1 C T 10: 80,909,043 (GRCm39) R25C probably damaging Het
Tmprss12 A G 15: 100,190,428 (GRCm39) E266G probably benign Het
Tpgs1 T A 10: 79,511,344 (GRCm39) V162D possibly damaging Het
Trpa1 C T 1: 14,944,648 (GRCm39) R1032Q probably benign Het
Tspan12 A G 6: 21,795,699 (GRCm39) Y164H probably damaging Het
Ubr4 T C 4: 139,135,274 (GRCm39) Y869H probably damaging Het
Vmn1r21 A G 6: 57,820,799 (GRCm39) I215T probably benign Het
Zan A T 5: 137,384,713 (GRCm39) S5104T unknown Het
Zfp318 T C 17: 46,722,980 (GRCm39) V1661A probably benign Het
Zfp365 C T 10: 67,724,772 (GRCm39) R372K probably damaging Het
Other mutations in Map4k4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00328:Map4k4 APN 1 40,043,976 (GRCm39) missense probably damaging 0.99
IGL00417:Map4k4 APN 1 40,053,692 (GRCm39) missense possibly damaging 0.92
IGL00516:Map4k4 APN 1 40,053,762 (GRCm39) missense probably damaging 1.00
IGL01545:Map4k4 APN 1 40,053,389 (GRCm39) splice site probably benign
IGL02092:Map4k4 APN 1 40,063,508 (GRCm39) missense probably damaging 1.00
IGL02092:Map4k4 APN 1 40,025,943 (GRCm39) missense probably benign 0.12
IGL02570:Map4k4 APN 1 40,019,739 (GRCm39) missense probably benign 0.06
IGL02626:Map4k4 APN 1 40,053,257 (GRCm39) splice site probably benign
IGL02993:Map4k4 APN 1 40,053,348 (GRCm39) missense probably damaging 0.98
IGL03178:Map4k4 APN 1 40,025,853 (GRCm39) missense possibly damaging 0.63
tank UTSW 1 40,044,024 (GRCm39) missense possibly damaging 0.93
IGL02835:Map4k4 UTSW 1 40,049,760 (GRCm39) missense probably damaging 0.99
R0496:Map4k4 UTSW 1 40,045,982 (GRCm39) missense probably damaging 0.99
R0498:Map4k4 UTSW 1 40,029,338 (GRCm39) missense probably benign 0.22
R0588:Map4k4 UTSW 1 40,044,024 (GRCm39) missense possibly damaging 0.93
R0674:Map4k4 UTSW 1 40,042,975 (GRCm39) missense probably damaging 1.00
R1205:Map4k4 UTSW 1 40,043,004 (GRCm39) missense probably damaging 1.00
R1349:Map4k4 UTSW 1 40,060,319 (GRCm39) missense probably damaging 1.00
R1615:Map4k4 UTSW 1 40,045,990 (GRCm39) splice site probably benign
R1763:Map4k4 UTSW 1 40,039,917 (GRCm39) splice site probably benign
R1893:Map4k4 UTSW 1 40,040,717 (GRCm39) missense probably benign 0.08
R2411:Map4k4 UTSW 1 40,046,656 (GRCm39) missense probably damaging 0.96
R2851:Map4k4 UTSW 1 40,039,915 (GRCm39) splice site probably benign
R2852:Map4k4 UTSW 1 40,039,915 (GRCm39) splice site probably benign
R2987:Map4k4 UTSW 1 40,025,925 (GRCm39) missense probably damaging 1.00
R3087:Map4k4 UTSW 1 40,060,242 (GRCm39) critical splice acceptor site probably null
R3688:Map4k4 UTSW 1 40,024,331 (GRCm39) splice site probably null
R4075:Map4k4 UTSW 1 40,062,622 (GRCm39) missense probably damaging 0.96
R4304:Map4k4 UTSW 1 40,013,132 (GRCm39) missense possibly damaging 0.74
R4564:Map4k4 UTSW 1 40,028,135 (GRCm39) missense probably damaging 1.00
R4569:Map4k4 UTSW 1 40,039,698 (GRCm39) missense probably damaging 1.00
R4613:Map4k4 UTSW 1 40,056,351 (GRCm39) missense probably benign 0.05
R4715:Map4k4 UTSW 1 40,058,724 (GRCm39) missense probably damaging 1.00
R4788:Map4k4 UTSW 1 40,043,076 (GRCm39) missense probably benign 0.01
R4926:Map4k4 UTSW 1 40,056,385 (GRCm39) missense probably damaging 1.00
R4943:Map4k4 UTSW 1 40,058,754 (GRCm39) missense probably damaging 0.99
R5033:Map4k4 UTSW 1 40,046,662 (GRCm39) missense probably damaging 0.99
R5177:Map4k4 UTSW 1 40,025,922 (GRCm39) missense probably damaging 1.00
R5297:Map4k4 UTSW 1 40,001,377 (GRCm39) missense probably damaging 1.00
R5844:Map4k4 UTSW 1 40,039,036 (GRCm39) splice site probably benign
R5952:Map4k4 UTSW 1 40,039,082 (GRCm39) unclassified probably benign
R6111:Map4k4 UTSW 1 40,050,822 (GRCm39) missense probably benign 0.00
R6125:Map4k4 UTSW 1 40,043,125 (GRCm39) missense possibly damaging 0.77
R6838:Map4k4 UTSW 1 40,015,882 (GRCm39) missense probably damaging 1.00
R6927:Map4k4 UTSW 1 40,050,842 (GRCm39) missense probably benign 0.00
R7008:Map4k4 UTSW 1 40,028,131 (GRCm39) missense probably benign 0.44
R7164:Map4k4 UTSW 1 40,013,132 (GRCm39) missense possibly damaging 0.74
R7195:Map4k4 UTSW 1 40,058,829 (GRCm39) missense possibly damaging 0.93
R7352:Map4k4 UTSW 1 40,001,387 (GRCm39) missense unknown
R7589:Map4k4 UTSW 1 40,060,251 (GRCm39) nonsense probably null
R7816:Map4k4 UTSW 1 40,053,368 (GRCm39) missense possibly damaging 0.53
R7869:Map4k4 UTSW 1 40,013,204 (GRCm39) missense unknown
R8013:Map4k4 UTSW 1 40,001,372 (GRCm39) missense unknown
R8145:Map4k4 UTSW 1 40,039,694 (GRCm39) missense
R8154:Map4k4 UTSW 1 40,060,302 (GRCm39) nonsense probably null
R8254:Map4k4 UTSW 1 40,045,835 (GRCm39) missense probably damaging 0.99
R8266:Map4k4 UTSW 1 40,050,813 (GRCm39) missense possibly damaging 0.53
R8375:Map4k4 UTSW 1 40,063,801 (GRCm39) missense possibly damaging 0.73
R8487:Map4k4 UTSW 1 40,028,136 (GRCm39) missense probably damaging 1.00
R8699:Map4k4 UTSW 1 40,015,910 (GRCm39) missense unknown
R8726:Map4k4 UTSW 1 40,043,142 (GRCm39) missense possibly damaging 0.95
R8907:Map4k4 UTSW 1 40,058,770 (GRCm39) missense probably damaging 0.97
R8956:Map4k4 UTSW 1 40,039,840 (GRCm39) missense probably benign 0.11
R8963:Map4k4 UTSW 1 40,039,740 (GRCm39) missense probably damaging 1.00
R9091:Map4k4 UTSW 1 40,042,923 (GRCm39) missense probably benign 0.02
R9234:Map4k4 UTSW 1 40,029,261 (GRCm39) missense unknown
R9270:Map4k4 UTSW 1 40,042,923 (GRCm39) missense probably benign 0.02
R9438:Map4k4 UTSW 1 40,045,952 (GRCm39) missense probably damaging 0.99
R9689:Map4k4 UTSW 1 40,058,722 (GRCm39) missense possibly damaging 0.95
R9771:Map4k4 UTSW 1 40,025,877 (GRCm39) missense unknown
Predicted Primers PCR Primer
(F):5'- TGCGGCACTACCACATTCAC -3'
(R):5'- ATGACTGGGAATTTGTTCCAACC -3'

Sequencing Primer
(F):5'- CTGGACATTCTTGGCTGAGCAC -3'
(R):5'- GACTGGGAATTTGTTCCAACCTTCTC -3'
Posted On 2014-06-23